Fundamental research on the treatment for pancreatic cancer by newly constructed oncolytic herpes simplex viruses

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We have developed a conditionally replication competent HSV-1 vector (d120.surv), a modified version of the mutant HSV-1 (d120), in which ICP4 is driven by survivin promoter. Further, we have developed another vector, d120. survE, in which 4f2 enhancer is included upstream of survivin promoter. In pancreatic cancer cell lines, the activity of 397 by survivin promoter was dependent on the expression of the survivin mRNA, and the survivin promoter was activated by irradiation. In the presence of 4f2 heavy chain enhancer protein, the survivin promoter was further activated by irradiation. Radio-resistant cell lines, Panc-1/Rad15 and AsPC-1/Rad10, showed stronger expression of survivin protein and stronger activity of survivin promoter. In pancreatic cancer cells, the titer of d120. surv, d120. survE and HrR3 was increased in a time dependent manner ; however, in survivin-negative HUVEC cells, the titer of d120. surv, d120. survE and HrR3 was not changed. By d120.surv, d120. survE and HrR3, the number of viable pancreatic cancer cells decreased in a MOI dependent manner. The oncolytic efficacy of the vectors was dependent on the activity of survivin promoter of each cancer cell.